The discovery of the 2'-5' oligoadenylates is connected with the study of the mechanisms of interferon action as the cellular response to virus infection [2]. The 5'-triphosphate of the (2'-5') oligoadenylate trimer plays a most important role in the antiviral mechanism induced by interferon [3]. It is generally regarded that activation of RNase L by 2-5A is key to the antiviral defense mechanisms. Interferon induces transcription of the enzyme 2-5A synthetase which produces 2',5'-linked oligoadenylates upon activation of double-stranded RNA.
Previously, the only known biochemical effect of 2-5A is activation of RNase L. This enzyme hydrolyzes mRNA and rRNA, thereby resulting in inhibition of protein synthesis. The activation of RNase L is transient unless 2-5A is continuously synthesized, since 2-5A is rapidly degraded. RNase L activation thus plays a critical role in inhibiting replication, and therefore in defending against infection by viruses.
Naturally occurring (2'-5')oligoadenylates (both 5'-phosphorylated and unphosphorylated) have shown different kinds of biological activity [4][5]. Analogues of the natural (2'-5')oligoadenylates have been synthesized to achieve new approaches to antiviral and antitumoral therapy [6-13]. Biological activities of 5'-phosphorylated (2'-5')oligoadenylates are connected with the functioning of the (2'-5')A system which leads to the inhibition of protein synthesis [3]. The mechanism of action of unphosphorylated (2'-5')oligoadenylates in many cases is still unknown. Recently, certain sugar-modified trimers of (2'-5')oligoadenylates were found to be inhibitors of HIV-1 reverse transcriptase (RT) [14-18].